Update: The following update relating to this announcement has been issued:

November 27, 2009 - See Notice NOT-MH-10-006 NIMH Announces Changes in NIMH Participation, As of January 8, 2010, NIMH will terminate or withdraw its participation from this FOA.

Program Announcement (PA) Number: PA-09-008

NOTICE: Applications submitted in response to this Funding
Opportunity Announcement (FOA) for Federal assistance must be submitted
electronically through Grants.gov (http://www.grants.gov)
using the SF424 Research and Related (R&R) forms and the SF424 (R&R)
Application Guide.

APPLICATIONS
MAY NOT BE SUBMITTED IN PAPER FORMAT.

This
FOA must be read in conjunction with the application guidelines included with
this announcement in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A
registration process is necessary before submission and applicants are highly
encouraged to start the process at least four (4) weeks prior to the grant
submission date. See Section IV.

Purpose. This funding opportunity announcement (FOA) solicits research grant
applications that propose to identify neurodevelopmental and
neuroendocrine mechanisms that impact emotional and cognitive development
and emerging psychopathology during adolescence,
utilizing animal models and human studies.

Mechanism
of Support.This FOA will utilize the NIH Research Project Grant
(R01) award mechanism and runs in parallel with an FOA of identical scientific scope, PA-09-009,
that encourages applications under the NIH Exploratory/Developmental (R21)
award mechanism.

Funds Available and Anticipated Number of Awards.Awards issued under this FOA
are contingent upon the availability of funds and the
submission of a sufficient number of meritorious applications.

Budget and
Project Period.The total
project period for an application submitted in response to this funding
opportunity may not exceed 5 years. Applicants for an R01 award are
not limited in dollars but need to reflect the actual needs of the
proposed project.

Eligible Institutions/Organizations.Institutions/organizations listed in Section III.1.A. are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). IncludeIndividuals with the skills,
knowledge, and resources necessary to carry out the proposed research are
invited to work with their institution/organization to develop an application
for support. Individuals from underrepresented racial and ethnic groups as well
as individuals with disabilities are always encouraged to apply for NIH
support.

Number
of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the
application.

Number
of Applications. Applicants may submit more than one application,
provided that each application is scientifically distinct.

Resubmissions.Applicants
may submit a resubmission application, but such application must include an
Introduction addressing the previous peer review critique (Summary Statement).

Adolescence is a developmental period encompassing dramatic hormonal,
physiological, and behavioral change. It is also a
uniquely important period for brain and psychological development during which
the symptoms of several mental disorders such as depression, schizophrenia,
eating disorders, and substance abuse are often first reported. This raises
questions of both moderating and mediating factors,
as well as opportunities for prevention and early treatment. A thorough
understanding of developmental neurobiology will help address these critical
health issues. To date, however, little is known about the underlying genetic, molecular and neurochemical systems that mediate
changes in the brain, or the degree to which hormonal signals initiate
neurodevelopmental and behavioral changes during adolescence.

Complicating our understanding of the developmental neurobiology of adolescence are sociocultural influences and considerable
variability in the age and rate at which individuals undergo pubertal
development. Pubertal changes occur earlier than previously and now generally
span ages 9 to 15 years. Early puberty in girls and
late puberty in boys constitute risk factors for adjustment problems. Which
changes in brain and behavior emerge as a function of chronological age and
which emerge as a function of puberty, and specifically, hormonal effects on
brain, are empirical questions.

NIMH-sponsored workshops and a recent report of the National Advisory
Mental Health Council addressed NIMH support of research in the area of
neurodevelopment relevant to adolescence and adolescent psychopathology.
Several areas of research opportunity were
identified. This initiative encourages basic and translational research to
establish understanding of the progression of brain development through
adolescence and the neurobiological processes that may contribute to risk for
mental disorders during this period; the
identification of appropriate targets to reduce risk; and the potential
development of preventive and treatment interventions. Basic research aimed at
identifying neurobiological changes in brain regions and circuits involved in
emotional and cognitive processes (emotional
regulation, executive functions, reward sensitivity and decision making)
including, for example, the amygdala, hippocampus, bed nucleus of the stria
terminalis, and prefrontal cortex, is strongly encouraged. The relative lack of appropriate cellular, molecular and genetic
tools has limited progress towards identifying neuroendocrine factors
contributing to juvenile brain development. Therefore, this initiative also
supports the development of novel approaches to assess,
visualize, and manipulate dynamic neuroendocrine signaling processes in brain
that contribute to alterations in emotional and cognitive function during
adolescence. The development and validation of model systems for exploring the
impact of specific hormonal changes in species that
adequately mimic aspects of human neuroendocrine function is also specifically
encouraged. In order to parse the relationships between brain development and
hormonal function in puberty and across adolescence, the search for neuroendocrine regulators of adolescent brain function must
occur in parallel with broader research efforts to identify the multiple
neurodevelopmental changes occurring in both sexes during this period. Thus,
this initiative encourages the expansion of basic
developmental neurobiological and behavioral studies into adolescence. Studies
in normal human adolescents and clinical populations are encouraged to explore
neurodevelopmental, neuroendocrine, behavioral, and environmental processes
contributing to changes in cognitive and affective
regulation, the expression of symptoms of psychopathology during this period,
and the identification of potential targets for preventive and treatment
interventions.

Research Scope

The purpose of this initiative is to encourage
research that will identify neurodevelopmental, molecular, connectivity, and hormonal changes that are critical in altering emotional and
cognitive development during adolescence. It is expected that this research
will contribute to understanding of normal
developmental processes and will help identify potential targets contributing
to psychopathology in adolescence, including targets for the development of
preventive or treatment interventions. The FOA encourages both basic
neurobiological studies using in vivo and cellular
model systems as well as studies in normal adolescent humans and in clinical
populations. Studies aimed at identifying the molecular signals regulating the
onset of puberty are not appropriate for this solicitation. However, studies focusing upon the impact of these signals in brain
systems regulating cognitive and emotional processes are appropriate. Research
with implications for the development of targeted intervention strategies is of
particular interest.

Listed below are examples of areas of interest.
Research relevant to this FOA is not limited to these examples.

Defining changes in brain neurobiology across adolescence

Define molecular and
cellular mechanisms regulating neural atrophy, pruning, and growth across adolescence and delineate how
these processes impact brain function and behavior in model systems relevant to mental illness.

Characterize and
define alterations in glial biology during adolescent brain development and
examine the specific roles of glial subpopulations
(astrocytes, oligodendrocytes and microglia) in modifying developmental
pathways and functional brain activity.

Apply cellular and
systems mapping techniques (both in vivo and in vitro) to identify changes in
neural organization and connectivity during
adolescent brain development. Areas of critical focus include neural circuitry
and systems integration in brain areas involved in emotional and cognitive
processes such as the amygdala, hippocampus, bed nucleus of the stria terminalis, and prefrontal cortex.

Apply conditional
mutagenesis strategies to explore the impact of molecular factors on
developmental trajectories in adolescence.

Characterize developmental changes in brain and behavioral stress responses
(including stressor-specific changes) and the relative persistence of exposure
effects from peri-adolescence into adulthood. Identify neurobiological and
hormonal mediators of these changes.

Assess whether adolescence represents a period of unique sensitivity
to experiential factors modulating the development of emotional circuits in
adulthood.

Identify circumstances under which hormone exposure (or lack thereof) during
adolescence has unique effects on the development of neural circuitry and
behavior.

Examine effects of
early life events (e.g., pre- and early post-natal experiences) on neural
changes induced by hormonal or environmental change
in adolescence and identify mechanisms through which such interactions occur.

Sex differences

Distinguish
hormone-dependent from non-hormone, sex-determined and other neurodevelopmental
effects in adolescence.

Distinguish genetic effects of sex chromosomes from organizational
and activational effects of gonadal hormones on brain development and
behavioral plasticity related to mood and cognition.

Develop, adapt, and
test appropriate behavioral measures of cognitive and emotional processes for
use across the pre-pubertal to adult developmental window in model systems and in humans.

Utilizing these
measures, examine the role of emotional intensity and valence on cognitive
function.

Examine potential
interaction of physical changes during puberty with psychological challenges in
adjusting to gender role conflicts emerging in
adolescence.

Develop standardized
measures to assess the emotional reaction to puberty and its relationship to
emerging psychopathology.

Normative human and clinical research opportunities

Design studies to
assess the rate and nature of brain changes
(structural, functional, metabolic using neuroimaging and other physiological
measures, e.g., sleep EEG) across adolescence in within subject designs.
Evaluate the relationship between brain changes and indices of pubertal
progression in both sexes.

Assess in clinical
populations the effects of alterations of normal
temporal patterns of endocrine development on brain function and behavior.

Evaluate
relationships between brain changes that occur in adolescence and genetic
determinants of such changes in both healthy development and clinical
disorders. Relate such changes to clinical symptoms
and to cognitive and emotional functioning.

Identify
pubertal/adolescent "triggers" of clinical disorders, including
adolescent onsets of disorder in previously healthy populations, as well as
emerging comorbidities in childhood onset disorders
(e.g., development of comorbid mood and anxiety disorders in ADHD).

Identify behaviors in
adolescence continuous with the later expression of symptoms of mental
disorders in adulthood. Determine which behavioral measures are sensitive to change in longitudinal or intervention studies.

Technology development and novel tool application opportunities

Apply selective
ligands and genetic tools to examine the impact of manipulating aspects of
neuroendocrine signaling during defined developmental
windows.

Develop techniques
requiring little or no radiation exposure for human studies in children ages 9
through 18 years of age to overcome the limitations
posed by the low radiation safety guidelines for minors that frequently
preclude the use of PET/SPECT for receptor occupancy studies.

Develop and validate
fMRI paradigms to evaluate the functional integrity of neurocircuitry
underlying emotional regulation, executive functions,
reward sensitivity, decision making and other domains known to be affected in
adolescent mental disorders.

Technology development applications need not be hypothesis driven.
Applications developing new technologies should validate the technologies before using them to test novel hypotheses
related to brain or behavior.

This FOA will use theNIH Research
Project Grant (R01)award mechanism.The Project
Director/Principal Investigator (PD/PI) will be solely responsible for
planning, directing, and executing the proposed project.

This
FOA uses “Just-in-Time” information concepts (see SF424 (R&R)
Application Guide). It also uses the modular as
well as the non-modular budget formats (seehttp://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or
less (excluding consortium Facilities and Administrative [F&A] costs)
should use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign
applicants must complete and submit budget requests using the Research &
Related Budget component.

2. Funds Available

Because the nature and scope of the proposed research
will vary from application to application, it is anticipated that the size and
duration of each award will also vary. Although the financial plans of the
IC(s) provide support for this program, awards pursuant to this funding
opportunity are contingent upon the availability of funds.

Facilities and Administrative (F&A) costs
requested by consortium participants are not included in the direct cost
limitation, see NOT-OD-05-004.

The decision of whether to apply for a grant with a
single PD/PI or multiple PDs/PIs grant is the responsibility of the
investigators and applicant organizations and should be determined by the
scientific goals of the project. Applications for grants with multiple PDs/PIs
will require additional information, as outlined in the instructions below. The
NIH review criteria for approach, investigators, and environment have been
modified to accommodate applications involving either a single PD/PI or
multiple PDs/PIs. When considering the multiple PD/PI option, please be aware
that the structure and governance of the PD/PI leadership team as well as the
knowledge, skills and experience of the individual PDs/PIs will be factored
into the assessment of the overall scientific merit of the application.
Multiple PDs/PIs on a project share the authority and responsibility for
leading and directing the project, intellectually and logistically. Each
PD/PI is responsible and accountable to the grantee organization, or, as
appropriate, to a collaborating organization, for the proper conduct of the
project or program, including the submission of required reports. For further
information on multiple PDs/PIs, please seehttp://grants.nih.gov/grants/multi_pi.

Applicants may submit
a resubmission application, but such application must include an Introduction addressing issues raised in the
previous critique (Summary Statement).

Applicants may submit
a renewal application.

Applicants may submit
more than one application, provided that each
application is scientifically distinct.

Section IV. Application and
Submission Information

To download a SF424 (R&R) Application Package and
SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for
this FOA, use the “Apply for Grant Electronically” button in this FOA or link
to http://www.grants.gov/Apply/ and
follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

The individual(s) designated as
PDs/PIs on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned
the PI role in the eRA Commons prior to the submission of the application.

Each PD/PI must
hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization
Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a
PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist
under one Commons account.

When multiple PDs/PIs are
proposed, all PDs/PIs at the applicant organization must be affiliated with
that organization. PDs/PIs located at another institution need not be
affiliated with the applicant organization, but must be affiliated with their
own organization to be able to access the Commons.

This registration/affiliation must
be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both
the PD(s)/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note
that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR
registration, that particular DUNS number and CCR registration are for the
individual reviewer only. These are different than any DUNS number and CCR
registration used by an applicant organization. Individual DUNS and CCR
registration should be used only for the purposes of personal reimbursement and
should not be used on any grant applications submitted to the Federal
Government.

Several
of the steps of the registration process could take four weeks or more.
Therefore, applicants should immediately check with their business official to
determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept
electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application
Information

Applicants must download the SF424 (R&R)
application forms and the SF424 (R&R) Application Guide for this FOA
through Grants.gov/Apply.

Note: Only the forms package directly attached to a
specific FOA can be used. You will not be able to use any other SF424 (R&R)
forms (e.g., sample forms, forms from another FOA), although some of the
"Attachment" files may be useable for more than one FOA.

Prepare
all applications using the SF424 (R&R) application forms and in accordance
with the SF424 (R&R) Application Guide for this
FOA through Grants.gov/Apply.

The
SF424 (R&R) Application Guide is critical to submitting a complete and
accurate application to NIH. Some fields within the SF424 (R&R) application
components, although not marked as mandatory, are required by NIH (e.g., the
“Credential” log-in field of the “Research & Related Senior/Key Person
Profile” component must contain the PD/PI’s assigned eRA Commons User ID).
Agency-specific instructions for such fields are clearly identified in the
Application Guide. For additional information, see “Frequently Asked Questions
– Application Guide, Electronic
Submission of Grant Applications.”

The
SF424 (R&R) application has several components. Some components are
required, others are optional. The forms package associated with this FOA in Grants.gov/APPLYincludes all applicable components, required and optional. A completed
application in response to this FOA includes the data in the following
components:

Proposed research
should provide special opportunities for furthering research programs through
the use of unusual talent, resources, populations, or environmental conditions
in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL
INSTRUCTIONS

Applications
with Multiple PDs/PIs

When
multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the
"Contact” PI, who will be responsible for all communication between the
PDs/PIs and the NIH, for assembling the application materials outlined below,
and for coordinating progress reports for the project. The contact PD/PI must
meet all eligibility requirements for PD/PI status in the same way as other
PDs/PIs, but has no other special roles or responsibilities within the project
team beyond those mentioned above.

Information
for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover
component. All other PDs/PIs should be listed in the Research &
Related Senior/Key Person component and assigned the project role of
“PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included
in the “Credential” field of the Research & Related Senior/Key Person
component. Failure to include this data field will cause the application
to be rejected.

All projects proposing
Multiple PDs/PIs will be required to include a new section describing the
leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating
multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI
Leadership Plan” [Section 14 of the Research Plan Component in the SF424
(R&R)], must be included. A rationale for choosing a multiple PD/PI
approach should be described. The governance and organizational structure of
the leadership team and the research project should be described, and should
include communication plans, process for making decisions on scientific
direction, and procedures for resolving conflicts. The roles and
administrative, technical, and scientific responsibilities for the project or
program should be delineated for the PDs/PIs and other collaborators.

If
budget allocation is planned, the distribution of resources to specific
components of the project or the individual PDs/PIs should be delineated in the
Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award (NoA).

Applications
Involving a Single Institution

When
all PDs/PIs are within a single institution, follow the instructions contained
in the SF424 (R&R) Application Guide.

Applications
Involving Multiple Institutions

When
multiple institutions are involved, one institution must be designated as the
prime institution and funding for the other institution(s) must be requested
via a subcontract to be administered by the prime institution. When submitting
a detailed budget, the prime institution should submit its budget using the
Research & Related Budget component. All other institutions should
have their individual budgets attached separately to the Research & Related
Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R)
Application Guide for further instruction regarding the use of the subaward
budget form.

When
submitting a modular budget, the prime institution completes the PHS398 Modular
Budget component only. Information concerning the consortium/subcontract
budget is provided in the budget justification. Separate budgets for each
consortium/subcontract grantee are not required when using the Modular budget
format. See Section 5.4 of the Application Guide for further instruction
regarding the use of the PHS398 Modular Budget component.

Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s)
and time, the application may be delayed in the review process or not reviewed.

Once an
application package has been successfully submitted through Grants.gov, any
errors have been addressed, and the assembled application has been created in
the eRA Commons, the
PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO)
have two weekdays (Monday – Friday, excluding Federal holidays) to view the
application image to determine if any further action is necessary.

If everything is acceptable, no further action is necessary. The
application will automatically move forward to the Division of Receipt and
Referral in the Center for Scientific Review for processing after two weekdays,
excluding Federal holidays.

Prior
to the submission deadline, the AOR/SO can “Reject” the assembled
application and submit a changed/corrected application within the two-day
viewing window. This option should be used if it is determined that some
part of the application was lost or did not transfer correctly during the
submission process, the AOR/SO will have the option to “Reject” the
application and submit a Changed/Corrected application. In these cases, please contact the eRA
Help Desk to ensure that the issues are addressed and corrected. Once
rejected, applicants should follow the instructions for correcting errors
in Section 2.12, including the requirement for cover letters on late
applications. The “Reject” feature should
also be used if you determine that warnings are applicable to your
application and need to be addressed now. Remember, warnings do not stop
further application processing. If an application submission results in
warnings (but no errors), it will automatically move forward after two weekdays
if no action is taken. Some warnings may need to be addressed later in the
process.

If
the two-day window falls after the submission deadline, the AOR/SO will have
the option to “Reject” the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or didn’t
transfer correctly during the submission process). The AOR/SO should first
contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course
of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to “Reject” the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH
late policy guidelines and may not be accepted. The reason for this delay
should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two days.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review, NIH. Incomplete applications
will not be reviewed.

There will
be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO
receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons
acknowledgments. Information related to the assignment of an application to a
Scientific Review Group is also in the Commons.

Note:
Since email can be unreliable, it is the responsibility of the applicant to
check periodically on their application status in the Commons.

The
NIH will not accept any application in response to this FOA that is essentially
the same as one currently pending initial merit review unless the applicant
withdraws the pending application. The NIH will not accept any application that
is essentially the same as one already reviewed. However, the NIH will accept a
resubmission application, but such application must include an Introduction
addressing the critique from the previous review.

All NIH awards are subject to the terms and
conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its
own risk and without NIH prior approval, incur obligations and expenditures to
cover costs up to 90 days before the beginning date of the initial budget
period of a new or renewal award if such costs: 1) are necessary to conduct the
project, and 2) would be allowable under the grant, if awarded, without NIH
prior approval. If specific expenditures would otherwise require prior
approval, the grantee must obtain NIH approval before incurring the cost. NIH
prior approval is required for any costs to be incurred more than 90 days
before the beginning date of the initial budget period of a new or renewal
award.

The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project.
See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

The applicant organization must include its DUNS
number in its Organization Profile in the eRA Commons. This DUNS number must
match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked
Questions – Application Guide, Electronic
Submission of Grant Applications.”

PHS398 Research Plan Component
Sections

Page limitations of the PHS398 Research Plan component
must be followed as outlined in the SF424 (R&R) Application Guide. While
each section of the Research Plan component needs to be uploaded separately as
a PDF attachment, applicants are encouraged to construct the Research Plan
component as a single document, separating sections into distinct PDF
attachments just before uploading the files. This approach will enable
applicants to better monitor formatting requirements such as page limits. All
attachments must be provided to NIH in PDF format, filenames must be included
with no spaces or special characters, and a .pdf extension must be
used.

All application instructions outlined in the SF424
(R&R) Application Guide are to be followed, incorporating
"Just-in-Time" information concepts, and with the following
additional requirements:

Specific Instructions for Applications
Requesting $500,000 (direct costs) or More per Year

Applicants requesting $500,000 or more in direct costs
for any year (excluding consortium F&A costs) must carry out the following
steps:

1) Contact the IC program staff at least 6 weeks
before submitting the application, i.e., as plans are being developed for the
study;

2)
Obtain agreement from the IC staff that the IC will accept the application for
consideration for award; and,

3) Include a cover letter with the application that
identifies the staff member and IC who agreed to accept assignment of the
application.

This policy applies to all new, renewal,
revision, or resubmission applications. See NOT-OD-02-004,
October 16, 2001.

Do not use the Appendix to circumvent the page
limitations of the Research Plan component. An application that does not comply
with the required page limitations may be delayed in the review process.

Resource Sharing
Plan(s)

NIH considers the sharing of unique research
resources developed through NIH-sponsored research an important means to
enhance the value and further the advancement of the research. When resources
have been developed with NIH funds and the associated research findings
published or provided to NIH, it is important that they be made readily available
for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to
sharing, this must be explained in the Resource Sharing section of the
application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(b) Sharing Model Organisms: Regardless of the
amount requested, all applications in which the development of model organisms
is anticipated are expectedto include a description of a
specific plan for sharing and distributing unique model organisms and related
resources, or state appropriate reasons why such sharing is restricted or not
possible (see Sharing
Model Organisms Policy, and NIH
Guide NOT-OD-04-042.)

(c) Genome-Wide Association
Studies (GWAS): Regardless of the amount requested, applicants
seeking funding for a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designatedGWAS
data repository, or provide an appropriate explanation why submission to the repository
is not possible. A genome-wide association study is defined as any study
of genetic variation across the entire genome that is designed to identify
genetic associations with observable traits (e.g., blood pressure or weight) or
the presence or absence of a disease or condition. For further
information see Policy
for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide
Association Studies(NOT-OD-07-088) and http://grants.nih.gov/grants/gwas/.

Foreign Applications (Non-domestic
[non-U.S.] Entities)

Indicate how the proposed project has specific relevance
to the mission and objectives of the NIH/IC and has the potential for
significantly advancing the health sciences in the United States.

Section V. Application Review
Information

1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria described below will be
considered in the review process.2. Review and
Selection Process

Applications submitted for this
funding opportunity will be assigned on the basis of established PHS referral
guidelines to the ICs for funding consideration.

Applications that are complete will be
evaluated for scientific and technical merit by (an) appropriate scientific
review group(s) in accordance with NIH peer review
procedures (http://grants1.nih.gov/grants/peer/) using the review criteria stated below.

As part of the scientific peer review, all
applications will:

Undergo a selection process in which
only those applications deemed to have the highest scientific and
technical merit, generally the top half of applications under review, will
be discussed and assigned a priority score;

Receive a written critique; and

Receive a second level of review by the appropriate national advisory council
or board.

Applications submitted in response to this funding
opportunity will compete for available funds with all other recommended
applications. The
following will be considered in making funding decisions:

Scientific and technical merit of the
proposed project as determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program
priorities.

The
goals of NIH supported research are to advance our understanding of biological
systems, to improve the control of disease, and to enhance health. In their
written critiques, reviewers will be asked to comment on each of the following
criteria in order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals. Each of these criteria will
be addressed and considered in assigning the overall score, and weighted as
appropriate for each application. Note that an application does not need to be
strong in all categories to be judged likely to have major scientific impact
and thus deserve a meritorious priority score. For example, an investigator may
propose to carry out important work that by its nature is not innovative but is
essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application
are achieved, how will scientific knowledge or clinical practice be advanced?
What will be the effect of these studies on the concepts, methods,
technologies, treatments, services, or preventative interventions that drive
this field?

Approach: Are
the conceptual or clinical framework, design, methods, and analyses adequately
developed, well-integrated, well-reasoned, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics? For applications designating multiple PDs/PIs, is
the leadership approach, including the designated roles and responsibilities,
governance, and organizational structure, consistent with and justified by the
aims of the project and the expertise of each of the PDs/PIs?

Innovation: Is the project original and
innovative? For example: Does the project challenge existing paradigms or
clinical practice; address an innovative hypothesis or critical barrier to
progress in the field? Does the project develop or employ novel concepts,
approaches or methodologies, tools, or technologies for this area?

Investigators: Are the PD/PIs and other key
personnel appropriately trained and well suited to carry out this work? Is the
work proposed appropriate to the experience level(s) of the principal
investigator(s) and other researchers? Do the PD/PIs and investigative team
bring complementary and integrated expertise to the project (if applicable)?

Environment: Do(es) the scientific
environment(s) in which the work will be done contribute to the probability of
success? Do the proposed studies benefit from unique features of the scientific
environment(s), or subject populations, or employ useful collaborative
arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria

In addition to the above criteria, the following items
will be considered in the determination of scientific merit and the rating:

Resubmission
Applications: Are the responses to
comments from the previous scientific review group adequate? Are the
improvements in the resubmission application appropriate?

Protection of Human Subjects from Research Risk: The involvement of human
subjects and protections from research risk relating to their participation in
the proposed research will be assessed. See the “Human Subjects Sections” of
the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated. See the “Human Subjects Sections” of the PHS398
Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals
are to be used in the project, the adequacy of the plans for their care and use
will be assessed. See the “Other Research Plan Sections” of the PHS398 Research
Plan component of the SF424 (R&R).

Biohazards: If materials or procedures are proposed that are potentially
hazardous to research personnel and/or the environment, determine if the
proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the
appropriateness of the requested period of support in relation to the proposed
research may be assessed by the reviewers. The priority score should not be
affected by the evaluation of the budget.

Applications from Foreign
Organizations: Whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions in other
countries that are not readily available in the United States or that augment
existing U.S. resources will be assessed.

2.C. Resource Sharing Plan(s)

When relevant, reviewers will
be instructed to comment on the reasonableness of the following Resource
Sharing Plans, or the rationale for not sharing the following types of
resources. However, reviewers will not factor the proposed resource sharing
plan(s) into the determination of scientific merit or priority score, unless
noted otherwise in the FOA. Program staff within the IC will be responsible for
monitoring the resource sharing.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section
IV.5., “Funding Restrictions.”

A final progress
report, invention statement, and Financial Status Report are required when an
award is relinquished when a recipient changes institutions or when an award is
terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding
opportunity and welcome the opportunity to answer questions from potential
applicants. Inquiries may fall into three areas: scientific/research (program),
peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Questions regarding scientific/research issues about basic neuroscience
related to normal adolescent brain biology in humans and animals, including cellular and molecular
neurobiology, developmental neuroendocrinology, systems neurobiology, cognitive, affective and social neuroscience, basic behavioral research, and tool and ligand development
may be directed to:

Questions regarding scientific/research issues
related to clinical phenomena in humans and animals, including studies that
delineate integrative models and neurobehavioral mechanisms relevant to the
development, treatment, or prevention of adolescent psychopathology, as well as susceptibility or resilience to mental
disorders in adolescence may be directed to:

Human
Subjects Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data
and Safety Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide
for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing
Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).Investigators should seek guidance from their
institutions, on issues related to institutional policies and local institutional
review board (IRB) rules, as well as local, State and Federal laws and
regulations, including the Privacy Rule. Reviewers will consider the data
sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in
advancing genome-wide association studies (GWAS) to identify common genetic
factors that influence health and disease through a centralized GWAS data
repository. For the purposes of this policy, a genome-wide association study is
defined as any study of genetic variation across the entire human genome that is
designed to identify genetic associations with observable traits (such as blood
pressure or weight), or the presence or absence of a disease or condition. All
applications, regardless of the amount requested, proposing a genome-wide
association study are expected to provide a plan for submission of GWAS data to
the NIH-designated GWAS data repository, or provide an appropriate explanation
why submission to the repository is not possible. Data repository management
(submission and access) is governed by the Policy for Sharing of Data Obtained
in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement. Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Inclusion of Women And Minorities in Clinical
Research:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical
Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them.

Required Education on the Protection of Human Subject
Participants:NIH policy requires education on the protection of human
subject participants for all investigators submitting NIH applications for
research involving human subjects and individuals designated as key personnel.
The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):Criteria for Federal funding of research on hESCs can
be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC line(s)
to be used in the proposed research. Applications that do not provide this
information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy,investigators
funded by the NIH must submit or have submitted for them to the
National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an
electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no
later than 12 months after the official date of publication. The
NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html).For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable
Health Information:The Department of Health and Human Services (HHS)
issued final modification to the "Standards for Privacy of Individually
Identifiable Health Information", the "Privacy Rule", on August
14, 2002. The Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection
of individually identifiable health information, and is administered and
enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All
applications and proposals for NIH funding must be self-contained within
specified page limitations. For publications listed in the appendix and/or
Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission
identification numbers must be used for publicly accessible on-line journal
articles. Publicly accessible on-line journal articles or PMC
articles/manuscripts accepted for publication that are directly relevant to the
project may be included only as URLs or PMC submission
identification numbers accompanying the full reference in either the
Bibliography & References Cited section, the Progress Report Publication
List section, or the Biographical Sketch section of the NIH grant application.
A URL or PMC submission identification number citation may be repeated in each
of these sections as appropriate. There is no limit to the number of URLs or
PMC submission identification numbers that can be cited.

Healthy People 2010:The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting
priority areas. This FOA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This program is described in the Catalog of Federal Domestic Assistance athttp://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive
Order 12372. Awards are made under the authorization of Sections 301 and 405 of
the Public Health Service Act as amended (42 USC 241 and 284) and under Federal
Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and
other considerations described in the NIH Grants
Policy Statement.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

Loan Repayment Programs:NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception,
infertility, and health disparities related areas. The LRP is an important
component of NIH's efforts to recruit and retain the next generation of
researchers by providing the means for developing a research career unfettered
by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged.
The periods of career award and LRP award may overlap providing the LRP
recipient with the required commitment of time and effort, as LRP awardees must
commit at least 50% of their time (at least 20 hours per week based on a 40
hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.